The international patent applications published as WO 2003/029232 and WO 2007/144006 disclose that the compound 4-[2-(4-methylphenylsulfanyl)phenyl]-piperidine has a pharmacological profile encompassing inhibition of the serotonin and noradrenalin reuptake, inhibition of the serotonin receptors 2A and 3 and adrenergic receptor α1A, and that said compound and salts thereof may be useful in the treatment of a range of indications, such as depression, anxiety and pain. Consequently, there is a need for processes for the manufacture of said compound which are easy, cheap and which provide a high yield.
WO 2003/029323 discloses a process wherein a tert-butoxycarbonyl protected piperidine-4-ol is transformed into an oxalate and then reduced by means of Bu3SnH to provide the desired compound after de-protection.
WO 2007/144006 discloses a process wherein ethoxycarbonyl protected piperidine-4-ol is obtained by reacting 2-(4-tolylsulfanyl)-phenyl bromide with N-carbethoxy-4-piperidone, which product is reduced by means of SiEt3H/TFA to provide the desired compound after de-protection. The process step in which the ethoxycarbonyl protected piperidine-4-ol is obtained is run at very low temperatures, i.e. −40° C. and the reduced intermediate is difficult to isolate as it does not readily crystallise.
WO 01/46147 discloses a method for reducing N-protected piperadine-4-ol by means of SiEt3H/TFA.